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Differential efficacy of empirical antibiotic therapy for febrile neutropenia in adolescent/young adult (AYA) and child patients

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Abstract

Survival rates in adolescent/young adult (AYA) patients with malignant diseases have improved with the introduction of pediatric-type chemotherapy; however, the higher frequency of treatment-related complications, including infections, remains a major challenge. We hypothesized that the efficacy of antibiotics may differ between AYA and younger children. We aimed to evaluate differences in the efficacy of antibiotics between them by retrospectively analyzing patients registered in previous first-line antibiotic comparative studies on febrile neutropenia (FN). Patients were classified into two groups: patients younger than 15 years of age (children group) and those aged 15 years or older (AYA group). The efficacy of antibiotic therapy was compared between groups. Success of therapy was defined as resolution of febrile episodes and clinical signs of infection within 120 h of the initiation of antibiotic therapy. A total of 818 febrile episodes in 204 patients were analyzed. Antibiotic therapy success rates were lower in the AYA group than in the children group (53.8 vs. 63.7%, P = 0.028), even when patients were restricted to those with bacteremia (11.8 vs. 41.4%, P = 0.025). However, mortality rates did not differ (0 vs. 0.5%, P = 1.000). The efficacy of first-line antibiotic therapy for FN was poorer in AYA patients than in child patients.

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References

  1. Boissel N, Auclerc MF, Lhéritier V, Perel Y, Thomas X, Leblanc T, et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003;21:774–80.

    Article  PubMed  Google Scholar 

  2. de Bont JM, Holt BV, Dekker AW, van der Does-van den Berg A, Sonneveld P, Pieters R. Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia. 2004;18:2032–5.

    Article  PubMed  Google Scholar 

  3. Hallböök H, Gustafsson G, Smedmyr B, Söderhäll S, Heyman M. Treatment outcome in young adults and children> 10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer. 2006;107:1551–61.

    Article  CAS  PubMed  Google Scholar 

  4. Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A, et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer. 2007;48:254–61.

    Article  PubMed  Google Scholar 

  5. Stock W, La M, Sanford B, Bloomfield CD, Vardiman JW, Gaynon P, et al. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children’s Cancer Group and Cancer and Leukemia Group B studies. Blood. 2008;112:1646–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Usvasalo A, Räty R, Knuutila S, Vettenranta K, Harila-Saari A, Jantunen E, et al. Acute lymphoblastic leukemia in adolescents and young adults in Finland. Haematologica. 2008;93:1161–8.

    Article  CAS  PubMed  Google Scholar 

  7. Hayakawa F, Sakura T, Yujiri T, Kondo E, Fujimaki K, Sasaki O, et al. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. Blood Cancer J. 2014;4:e252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Woods WG, Franklin AR, Alonzo TA, Gerbing RB, Donohue KA, Othus M, et al. Outcome of adolescents and young adults with acute myeloid leukemia treated on COG trials compared to CALGB and SWOG trials. Cancer. 2013;119:4170–9.

    Article  CAS  PubMed  Google Scholar 

  9. Tomizawa D, Watanabe T, Hanada R, Horibe K, Horikoshi Y, Iwamoto S, et al. Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols. Int J Hematol. 2015;102:318–26.

    Article  PubMed  Google Scholar 

  10. Patte C, Ribrag V, Brugières L. Non Hodgkin’s lymphoma in adolescents. Bull Cancer. 2007;94:339–48.

    PubMed  Google Scholar 

  11. Sandlund JT. Should adolescents with NHL be treated as old children or young adults? Hematol Am Soc Hematol Educ Program. 2007;2007:297–303.

    Google Scholar 

  12. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27:911–8.

    Article  CAS  PubMed  Google Scholar 

  13. Pichler H, Reismüller B, Steiner M, Dworzak MN, Pötschger U, Urban C, et al. The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment-related mortality and not an increased relapse rate—a population-based analysis of 25 years of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group. Br J Haematol. 2013;161:556–65.

    Article  PubMed  Google Scholar 

  14. Creutzig U, Büchner T, Sauerland MC, Zimmermann M, Reinhardt D, Döhner H, et al. Significance of age in acute myeloid leukemia patients younger than 30 years: a common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG 92/99 and AMLSG HD93/98A. Cancer. 2008;112:562–71.

    Article  PubMed  Google Scholar 

  15. Rubnitz JE, Pounds S, Cao X, Jenkins L, Dahl G, Bowman WP, et al. Treatment outcome in older patients with childhood acute myeloid leukemia. Cancer. 2012;118:6253–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Canner J, Alonzo TA, Franklin J, Freyer DR, Gamis A, Gerbing RB, et al. Differences in outcomes of newly diagnosed acute myeloid leukemia for adolescent/young adult and younger patients: a report from the Children’s Oncology Group. Cancer. 2013;119:4162–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Creutzig U, van den Heuvel-Eibrink MM, Gibson B, Dworzak MN, Adachi S, de Bont E, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood. 2012;120:3187–205.

    Article  CAS  PubMed  Google Scholar 

  18. Sarashina T, Kobayashi R, Yoshida M, Toriumi N, Suzuki D, Sano H, et al. A randomized trial of cefozopran versus cefepime as empirical antibiotic treatment of febrile neutropenia in pediatric cancer patients. Pediatr Blood Cancer. 2014;61:1992–5.

    Article  CAS  PubMed  Google Scholar 

  19. Sano H, Kobayashi R, Suzuki D, Kishimoto K, Yasuda K, Kobayashi K. Comparison between piperacillin/tazobactam and cefepime monotherapies as an empirical therapy for febrile neutropenia in children with hematological and malignant disorders: a prospective, randomized study. Pediatr Blood Cancer. 2015;62:356–8.

    Article  CAS  PubMed  Google Scholar 

  20. Sano H, Kobayashi R, Suzuki D, Hori D, Kishimoto K, Kobayashi K. A prospective randomized trial comparing piperacillin/tazobactam with meropenem as empirical antibiotic treatment of febrile neutropenic children and adolescents with hematologic and malignant disorders. Pediatr Blood Cancer. 2017;64:e26360.

    Article  CAS  Google Scholar 

  21. Veal GJ, Hartford CM, Stewart CF. Clinical pharmacology in the adolescent oncology patient. J Clin Oncol. 2010;28:4790–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:427–31.

    Article  PubMed  Google Scholar 

  24. Kobayashi R, Suzuki D, Sano H, Kishimoto K, Yasuda K, Kobayashi K. Effect of meropenem with or without immunoglobulin as second-line therapy for pediatric febrile neutropenia. Pediatr Int. 2014;56:526–9.

    Article  CAS  PubMed  Google Scholar 

  25. Kobayashi R, et al. Meropenem versus piperacillin/tazobactam with or without immunoglobulin as second-line therapy for febrile neutropenia in pediatric patients. J Microbiol Immunol Infect. 2017. https://doi.org/10.1016/j.jmii.2017.06.005

    Article  PubMed  Google Scholar 

  26. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  PubMed  Google Scholar 

  27. Pulte D, Gondos A, Brenner H. Trends in survival after diagnosis with hematologic malignancy in adolescence or young adulthood in the United States, 1981–2005. Cancer. 2009;115:4973–9.

    Article  PubMed  Google Scholar 

  28. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541–52.

    Article  CAS  PubMed  Google Scholar 

  29. Scammon RE. The measurement of the body in childhood. In: Harris JA, Jackson CM, Paterson DG, Scammon RE, editors. The measurement of man. Minneapolis: University of Minnesota Press; 1930. pp. 173–215.

    Google Scholar 

  30. Kobayashi R, Kaneda M, Sato T, Ichikawa M, Suzuki D, Ariga T. The clinical feature of invasive fungal infection in pediatric patients with hematologic and malignant diseases: a 10-year analysis at a single institution at Japan. J Pediatr Hematol Oncol. 2008;30:886–90.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

HS, RK, and KK planned the study, interpreted the data, and wrote the manuscript. DS, KK, DH, SM, MY, TS, and NT helped with data collection and interpretation.

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Correspondence to Hirozumi Sano.

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The authors have no conflicts of interest to declare.

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Sano, H., Kobayashi, R., Suzuki, D. et al. Differential efficacy of empirical antibiotic therapy for febrile neutropenia in adolescent/young adult (AYA) and child patients. Int J Hematol 108, 543–549 (2018). https://doi.org/10.1007/s12185-018-2503-6

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  • DOI: https://doi.org/10.1007/s12185-018-2503-6

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